1. Field of the Invention
The present invention relates to a method for treatment of brain injury and neuronal disorders, such as epilepsy, by administration of an effective amount of nefiracetam.
2. Discussion of the Background
Traumatic brain injury, as well as neuronal disorders with common pathological features, such as stroke and epilepsy, can have devastating effects on a person, both short-term and long-term. Traumatic brain injury is often associated with cerebral concussion. Cerebral concussion is a traumatically induced derangement of the nervous system, characterized clinically by immediate and transient impairment of consciousness and is generally not associated with remarkable gross anatomical changes. Even moderate levels of concussive human head injury, not requiring prolonged hospitalization, can result in persistent neurological disturbances often lasting for months. These disturbances often include dizziness and balance problems, and fine motor skill dysfunction. Lyeth et al, Brain Research, 452, 39-48 (1988).
Traumatic brain injury is known to be a biphasic process. The first phase, the excitatory phase, occurs immediately upon injury. During this phase there is great neuronal excitation due to the trauma. Following the excitatory phase is the recovery phase, during which the neuronal excitation has abated and the job of repair has begun. Most often with traumatic brain injury, the excitatory phase is associated with increased intracranial pressure (ICP), with fluctuations of ICP over several days or more. Patients in the excitatory phase must typically be cared for in the intensive care unit of a hospital. Once the ICP has been stabilized and the patient can be removed from intensive care, the patient is typically entering into the recovery phase.
Traumatic brain injury produces an acute neuronal depolarization and an extensive release of neurotransmitters. The resulting excessive receptor activation may produce abnormal neurotransmitter-receptor interactions which contribute to the pathophysiology associated with experimental traumatic brain injury. Both the cholinergic and glutamatergic receptor systems have been documented to play a prominent role in the receptor-mediated pathophysiology of traumatic brain injury. Prior attempts to treat traumatic brain injury have focused on administration of antagonists of these cholinergic or glutamatergic receptors (such as the AMPA-glutamate receptor, wherein AMPA represents xcex1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) as early as possible after the occurrence of the injury. (See Hamm et al, Cognitive Brain Research, 1, 223-226 (1993) and Lyeth et al, Brain Research, 452, 39-48 (1988)). The goal of these studies was to add the antagonist during the excitatory phase of the injury process during the period of high receptor activity in an attempt to minimize the damage occurring to the neuronal tissue. Unfortunately, such attempts were not successful.
Accordingly, one object of the present invention is to provide a method effective for the treatment of brain injuries, particularly traumatic brain injury.
A further object of the present invention is to provide a method for treatment of neuronal disorders such as epilepsy.
These and other objects of the present invention have been satisfied by the discovery of a method for the treatment of neuronal disorders and brain injury comprising:
administering to a subject in need thereof, an effective amount of nefiracetam.